Recruiting
Phase 1
Phase 2

Cyclophosphamide, Sirolimus, Mycophenolate Mofetil

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05436418

Conditions

Peripheral Blood Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

Sex: All

Age: 12 - 70+

Healthy Volunteers: Accepted

Interventions

Melphalan

Sirolimus

Total Body Irradiation (TBI)

Cyclophosphamide

Mycophenolate Mofeti

Study Details

Brief summary:

Background:

Blood cancers (such as leukemias or lymphomas) often do not respond to standard treatments. A transplant of blood stem cells from a healthy donor can help people with these cancers. Sometimes these transplants cause serious side effects, including a common immunologic problem called graft-versus-host disease. A drug called cyclophosphamide given early after the transplant (post-transplantation cyclophosphamide, PTCy) can reduce these complications. But sometimes this drug has its own negative effects. Furthermore, studies in mice suggest that an intermediate, rather than very high, dose of this drug may best protect against graft-versus-host disease.

Objective:

To find out if a lower dose of PTCy is more helpful for people who undergo blood stem cell transplants.

Eligibility:

People aged 18 and older who have a blood cancer and are eligible for a transplant of blood stem cells from another person. Healthy donors are also needed but must be related to the individual needing the transplant.

Design:

Participants will undergo screening. Transplant recipients will have imaging scans and tests of their heart and lung function. They will be assessed for the status of their cancer, including bone marrow taken from their pelvis and possibly also scans and/or fluid drawn from the spine depending on the disease type.

Donors will be screened for general health. They will give several tubes of blood. They will give an oral swab and saliva and stool samples for research.

Recipients will be in the hospital at least 4 to 6 weeks.

They will have a temporary catheter inserted into a vein in the chest or neck. Medications will be given and blood will be drawn through the catheter.

The transplanted stem cells will be given through the catheter. Participants will receive medications both before and after the transplant.

Participants will return to the clinic at least once a week for 3 months after leaving the hospital. Follow-up visits will continue periodically for 5 years.

Conditions

Peripheral Blood Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

Study ID

NCT05436418

Start date

Nov 18, 2022

Status verified date

Jun 9, 2026

Completion date

Jun 25, 2028

Anticipated

Primary completion date

Jun 25, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12 - 70+

Healthy Volunteers: Accepted

  • INCLUSION CRITERIA:

Recipient

  • Participants must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation limited to one of the following:

  • Acute myeloid leukemia (AML) of intermediate or adverse risk disease by the 2017 European LeukemiaNet criteria in first morphologic complete remission (<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease)
  • AML of any risk in second or subsequent morphologic complete remission
  • Acute lymphoblastic leukemia in first or subsequent complete remission
  • Myelodysplastic syndrome of intermediate or higher score by the Revised International Prognostic Scoring System (IPSS-R)
  • Primary myelofibrosis of intermediate-2 or higher risk by the DIPSS
  • Chronic myelomonocytic leukemia
  • Chronic myelogenous leukemia resistant to or intolerant of >= 3 tyrosine kinase inhibitors or with history of accelerated phase or blast crisis
  • B-cell lymphoma including Hodgkin lymphoma that has relapsed within 1 year of completion of primary treatment, relapsed after autologous transplantation, or has progressed through at least 2 lines of therapy
  • Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHV or refractory to or intolerant of both BTK and PI3K inhibitors
  • Mature T or NK neoplasms as defined in the WHO guidelines of sufficient type and severity for allogeneic HCT based on the Prognostic Index for T-cell lymphoma (PIT) score of low-intermediate risk or higher or on recently published clinical practice guidelines
  • Hematologic malignancy of dendritic cell or histiocytic cell type
  • Multiple myeloma, stage III, relapsing after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD)
  • Age >= 50 years or age 18-49 years and also meeting one of the following criteria:

  • Prior myeloablative HCT
  • Prior exposure to inotuzumab, gemtuzumab, or other agent that increases the risk for sinusoidal obstruction syndrome.
  • Hematopoietic Cell Transplantation- Comorbidity Index (HCT-CI) >= 3
  • Karnofsky performance score <80
  • Co-morbidity considered by the treating physician to be exclusionary of myeloablative conditioning
  • At least one potentially suitable HLA-haploidentical or 10/10 (HLA-A, B, C, DR, DQ) related or unrelated donor for HCT
  • Karnofsky performance score >= 70
  • Adequate organ function defined as possessing all of the following:

  • Cardiac ejection fraction >= 45% by 2D ECHO;
  • Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of >= 50% predicted;
  • Estimated serum creatinine clearance of >= 60 ml/minute/1.73m\^2 calculated using eGFR in the clinical lab;
  • Total bilirubin <= 2X the upper limit of normal;
  • Alanine aminotransferase and aspartate aminotransferase <= 3X the upper limit of normal.
  • Individuals of child-bearing potential (IOCBP) and participants who can father children must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-transplant.
  • IOCBP must have a negative serum or urine pregnancy test within 7 days prior to initiation of conditioning regimen.
  • Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Recipient

  • Participants who are receiving any other investigational agents. Prior experimental therapies must have been completed at least 2 weeks prior to the date of beginning conditioning.
  • Active nursing.
  • Active malignancy of non-hematopoietic type (excluding non-melanoma skin cancers) which is: metastatic, or relapsed/refractory to treatment, or locally advanced and not amenable to curative treatment, or limited disease treated with curative intent treatment within the last 2 years. This excludes non-melanoma skin cancers.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents.
  • Uncontrolled intercurrent illness (e.g., severe endocrinopathy, disseminated intravascular coagulation, profound electrolyte disturbance, active infectious hepatitis, uncontrolled dental infection) that in the opinion of the Site PI would make it unsafe to proceed with transplantation.

INCLUSION CRITERIA:

Donor

  • Related (age >=12) and unrelated (age >=18) donors deemed eligible (i.e., evaluated at NIH, COH, and FHCC in accordance with existing institutional Standard Policies and Procedures or evaluated per the standards required by the IRB of the National Marrow Donor Program or applicable registry), and willing to donate research samples will be included.
  • Ability of participant or parent/legal guardian to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Donor

None

Study Design

Enrollment

260 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

no intervention: Donors (Haplo HCT)

Research on collected samples

no intervention: Donors (Matched HCT)

Research on collected samples

experimental: Phase I Dose De-escalation (Haplo HCT)

PTCy at de-escalating doses to assess for safety and determine Phase II dose

experimental: Phase I Dose De-escalation (Matched HCT)

PTCy at de-escalating doses to assess for safety and determine Phase II dose

experimental: Phase I Pilot for Comparative Data (Haplo HCT)

Standard PTCy 50 mg/kgday on days +3 and +4

experimental: Phase I Pilot for Comparative Data (Matched HCT)

Standard PTCy 50 mg/kg/day on days +3 and +4

experimental: Phase II Efficacy (Haplo HCT)

PTCy at shortest duration, safe dose (from Phase I)

experimental: Phase II Efficacy (Matched HCT)

PTCy at shortest duration, safe dose (from Phase I)

Interventions

Melphalan

Matched HCT: 100 mg/m\^2 IV on day -2 over 30 minutes. Haplo HCT:

100 mg/m\^2 IV on day -6 over approximately 20-30 minutes.

Sirolimus

Sirolimus: Loading dose of 6 mg orally given on day +5 (calculated based on actual body weight, max initial dose 6 mg)\^d, then maintenance dose starting at 2 mg orally daily on day +6 with dose adjustments to maintain a trough of 5-12 ng/ml, continued through day +80 with no taper. Doses should be modified as appropriate for drug interactions and may be modified based on institutional practice.

Total Body Irradiation (TBI)

Haplo HCT only: A dose of 200 cGy will be administered on day -1.

Cyclophosphamide

based on dose level being tested (50, 35, 25, or 15 mg/kg) IV once daily over 2 hours on days +3 and +4. Cyclophosphamide will be dosed according to ideal body weight. Cyclophosphamide infusion on days +3 should be started between 70-74 hours after the start of the PBSC infusion. Cyclophosphamide infusion on day +4 should be started between 94-98 hours after the start of the bone marrow infusion.

Mycophenolate Mofeti

15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. Dosing will be according to actual body weight.

Fludarabine

Matched HCT: 25 mg/m\^2/day infused IV over 60 minutes from day -7 to day -3. Haplo HCT: 40 mg/m\^2/day infused IV over approximately 30-60 minutes from day -5 to day -2

Allogeneic HSCT

Stem cell transplant

Mesna

equal to the cyclophosphamide dose (50, 35, 25, or 15 mg/kg) as IV infusion concomitant with cyclophosphamide. Mesna is dosed in the same way as cyclophosphamide regarding ideal vs. actual body weight.b Dosing may be modified based on institutional standard practice.

Filgrastim

begins on day +5 at a dose of 5 mcg/kg/day (actual body weight; dose rounding is permitted e.g., nearest vial or syringe size) and is administered daily subcutaneously or IV until the absolute neutrophil count is > 1000 cells/mm3 for three days or > 5000 for one day.

Primary outcome measure

  • Phase II: Evaluate the efficacy of PTCy, at the lowest dose determined for each HLA-matching arm from phase I, as assessed by 1-year GVHD-free relapse-free survival (GRFS) rate. [ Time Frame: 1 year ]
  • Phase I: Determine the lowest effective dose of PTCy in combination with sirolimus and mycophenolate mofetil as GVHD prophylaxis after reduced intensity conditioning and PBSCT, as assessed by primary graft failure AND Grade III-IV acute GVHD as ... [ Time Frame: 60 days ]

Central Contacts and Locations

Central contacts

Amy H Chai

(240) 858-3755amy.chai@nih.gov

Christopher G Kanakry, M.D.

(240) 760-6171christopher.kanakry@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Jun 11, 2026

Last verified

Jun 9, 2026

Keywords

  • Reduced Intensity Conditioning
  • Systemic Immunosuppressive Therapy
  • Hematologic Malignancy
  • Acute Myeloid Leukemia
  • Calcineurin Inhibitor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-06-11.